Abstract

Background

Microparticles (MPs) are membrane vesicles which are released from normal and malignant
cells following a process of budding and detachment from donor cells. MPs contain
surface antigens, proteins and genetic material and serve as vectors of intercellular
communication. MPs comprise the major source of systemic RNA including microRNA (miRNA),
the aberrant expression of which appears to be associated with stage, progression
and spread of many cancers. Our previous study showed that MPs carry both transcripts
and miRNAs associated with the acquisition of multidrug resistance in cancer.

Results

Herein, we expand on our previous finding and demonstrate that MPs carry the transcripts
of the membrane vesiculation machinery (floppase and scramblase) as well as nucleic acids encoding the enzymes essential for microRNA biogenesis
(Drosha, Dicer and Argonaute). We also demonstrate using microarray miRNA profiling analysis, the selective packaging
of miRNAs (miR-1228*, miR-1246, miR-1308, miR-149*, miR-455-3p, miR-638 and miR-923) within the MP cargo upon release from the donor cells.

Conclusions

These miRNAs are present in both haematological and non-haematological cancer cells
and are involved in pathways implicated in cancer pathogenesis, membrane vesiculation
and cascades regulated by ABC transporters. Our recent findings reinforce our earlier
reports that MP transfer ‘re-templates’ recipient cells so as to reflect donor cell
traits. We now demonstrate that this process is likely to occur via a process of selective
packaging of nucleic acid species, including regulatory nucleic acids upon MP vesiculation.
These findings have significant implications in understanding the cellular basis governing
the intercellular acquisition and dominance of deleterious traits in cancers.